The Role of Abdominal Surgery in Refractory Immune Checkpoint Inhibitor Enterocolitis: A Case Report.

This article describes the case of a 73-year-old patient with grade 3 immune checkpoint inhibitor (ICI)-induced enteritis. Five different immunosuppressive agents (glucocorticoids, high-dose infliximab, methotrexate, mycophenolate mofetil, and vedolizumab) were administered, however, with no clinical or radiographical benefit. A laparotomy was performed, as the patient showed signs of intestinal obstruction, with a segmental resection of the ileal loop. Biopsy results showed multiple fibrotic strictures. The current treatment guidelines for ICI enterocolitis only include drugs as a treatment option. Nevertheless, it remains important to consider early surgical intervention in order to avoid serious complications due to persistent and pronounced inflammation. The current case highlights the importance of surgery as a treatment modality in the multidisciplinary approach for ICI-induced enteritis, which should be taken into consideration after second- or third-line treatment.

Viral clade is associated with severity of symptomatic genotype 3 hepatitis E virus infections in Belgium, 2010-2018.

BACKGROUND & AIMS: HEV genotype (gt) 3 infections are prevalent in high-income countries and display a wide spectrum of clinical presentations. Host - but not viral - factors are reported to be associated with worse clinical outcomes. METHODS: Demographic, clinical, and biochemical data laboratory-confirmed HEV infections (by PCR and/or a combination of IgM and IgG serology) at the Belgian National Reference Centre between January 2010 and June 2018 were collected using standardised case report forms. Genotyping was based on HEV open reading frame 2 sequences. Serum CXCL10 levels were measured by a magnetic bead-based assay. H&E staining was performed on liver biopsies. RESULTS: A total of 274 HEV-infected individuals were included. Subtype assignment was possible for 179/218 viraemic cases, confirming gt3 as dominant with an almost equal representation of clades abchijklm and efg. An increased hospitalisation rate and higher peak serum levels of alanine aminotransferase, bilirubin, and alkaline phosphatase were found in clade efg-infected individuals in univariate analyses. In multivariable analyses, clade efg infections remained more strongly associated with severe disease presentation than any of the previously identified host risk factors, being associated with a 2.1-fold higher risk of hospitalisation (95% CI 1.1-4.4, p = 0.034) and a 68.2% higher peak of bilirubin levels (95% CI 13.3-149.9, p = 0.010), independently of other factors included in the model. In addition, acute clade efg infections were characterised by higher serum CXCL10 levels (p = 0.0005) and a more pronounced liver necro-inflammatory activity (p = 0.022). CONCLUSIONS: In symptomatic HEV gt3 infections, clade efg is associated with a more severe disease presentation, higher serum CXCL10 levels, and liver necro-inflammatory activity, irrespective of known host risk factors. CLINICAL TRIAL REGISTRATION: The protocol was submitted to clinicaltrials.gov (NCT04670419). IMPACT AND IMPLICATIONS: HEV genotype (gt) 3 infections display a wide spectrum of clinical presentations currently ascribed to host factors. Here we examined the role of viral factors on liver disease outcomes by combining viral phylogeny with clinical, biochemical, cytokine, and histological data from 274 Belgian adults infected with HEV presenting between 2010 and 2018. HEV gt 3 clade efg infections were associated with a more severe disease presentation, higher serum CXCL10 levels and liver necro-inflammatory activity, irrespective of known host risk factors. HEV gt3 clade-dependent clinical outcomes call for broad HEV gt3 subtyping in clinical practice and research to help identify those at higher risk for worse outcomes and to further unravel underlying virus-host interactions.

Real-life multi-center retrospective analysis on nivolumab in difficult-to-treat patients with advanced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The landscape of the systemic treatment for advanced HCC is changing quickly, and recently, the standard of care became either atezolizumab plus bevacizumab or tremelimumab plus durvalumab in the single tremelimumab regular interval durvalumab regimen. Nivolumab monotherapy has proven to be effective sometimes for advanced HCC and could be a valuable treatment option for patients outside current treatment indications and reimbursement criteria for the standard of care. This is a particular population of interest. AIM: To evaluate the real-world effectiveness of nivolumab monotherapy in patients with advanced HCC who are not eligible for other treatment. METHODS: We conducted a retrospective, multicentric study including 29 patients with advanced HCC from 3 Belgian tertiary hospitals. All patients had had prior chemotherapy or were intolerant or ineligible for treatments. All study subjects received nivolumab 3 mg/kg in monotherapy, administered once every two weeks intravenously. Treatment continued until disease progression, severe adverse events or death. Data were retrieved from patients' medical records. The outcome parameters such as radiological response according to response evaluation criteria in solid tumors (RECIST) criteria, the biological response through the evolution of the alpha-fetoprotein (AFP) level, and clinical response considering both the Child-Pugh (CP) score and the World Health Organization (WHO) performance status (PS) were reported. A safety profile was also reported. Statistical analysis was performed using the SPSS Statistics 27 statistical software package. RESULTS: The radiological overall response rate (defined as complete or partial response according to the immune RECIST and modified RECIST criteria) to nivolumab monotherapy was 24.1%. The biological overall response rate (defined as a decrease of ≥ 25% in AFP blood level) was 20.7%. Radiological and biological responses were significantly associated both with each other (P < 0.001) and with overall survival (P < 0.005 for radiological response and P < 0.001 for biological response). Overall survival was 14.5 mo (+/- 2.1), and progression-free survival was 10.9 mo (+/- 2.3). After 4 mo of treatment, 78.3% of patients remained clinically stable or even showed improvement in WHO PS. Grade 3 adverse events occurred in 17.2% of patients, none had grade 4 adverse events, and no patients ceased nivolumab due to adverse events. CONCLUSION: Nivolumab monotherapy is a good treatment choice in frail patients with HCC who are ineligible for the standard of care or other validated systemic treatments.

Resolution of a hepatoduodenal fistula after nivolumab treatment in a patient with hepatocellular carcinoma: challenges in immunotherapy.

Hepatocellular carcinoma is the fourth leading cause of cancer-related death worldwide, with limited treatment options for patients with advanced hepatocellular carcinoma. Beyond standard systemic therapy with multikinase inhibitors, recent studies demonstrate the potential for a robust and durable response with immune checkpoint inhibition in subsets of patients with hepatocellular carcinoma.We present a case of an 83-year-old male patient with the diagnosis of a multifocal hepatocellular carcinoma. A hepatoduodenal fistula developed under treatment with sorafenib which necessitated treatment interruption. Therefore, a switch to second line therapy with immunotherapy nivolumab was made and supportive enteral nutrition was started. This led to a spectacular oncological response, with complete resolution of the hepatoduodenal fistula. To our knowledge this is the first case which describes the involution of a fistula in a hepatocellular carcinoma under treatment with nivolumab.